Methods for using triazolo-pyrazinyl soluble guanylate cyclase activators in fibrotic disorders

1. A method for treating or preventing systemic sclerosis; the method comprising administering a therapeutically effective amount of a compound having structural Formula I:

or a pharmaceutically acceptable salt thereof to a patient in need of such treatment, wherein:

C* indicates a potential chiral carbon atom;

R 1 is

(1) hydrogen

(2) (C 1-6 )alkyl,

(3) halo(C 1-6 )alkyl,

(4) (C 1-6 )alkyl-O—,

(5) halo(C 1-6 )alkyl-O—,

(6) (C 1-6 )alkyl-NH—,

(7) halo(C 1-6 )alkyl-NH—,

(8) —(C 1-3 )alkyl-(C 3-7 )cycloalkyl,

(9) —(C 1-3 )alkyl-aryl, wherein aryl is unsubstituted or substituted by one, two, or three R 7 ,

(10) aryl unsubstituted or substituted by one, two, or three R 7 ,

(11) (C 3-7 )cycloalkyl, or

(12) —(C 1-3 )alkyl-heteroaryl wherein the heteroaryl is a 5- or 6-membered ring containing one, two, or three heteroatoms independently selected from the group consisting of N, O, and S, and wherein heteroaryl is unsubstituted or substituted by one, two, or three R 7 ;

R 2 is

(1) (C 1-3 )alkyl, or

(2) (C 3-7 )cycloalkyl;

R 3 is

(1) aryl unsubstituted or substituted by one, two, or three R 6 ,

(2) five- or six-membered heteroaryl containing one, two, or three heteroatoms independently selected from N, O and S, wherein heteroaryl is unsubstituted or substituted by one, two, or three R 6 ,

(3) (C 1-3 )alkyl, or

(4) (C 3-7 )cycloalkyl;

R 4 is

(1) hydrogen,

(2) (C 1-3 )alkyl,

(3) halo(C 1-3 )alkyl, or

(4) (C 3-7 )cycloalkyl;

R 5 is

(1) hydrogen,

(2) hydroxy,

(3) —N(R 8a )(R 8b ),

(4) —COOH,

(5) —C(O)NH 2 ,

(6) (C 1-3 )alkyl,

(7) (C 3-7 )cycloalkyl, or

(8) four- to six-membered monocyclic heterocyclyl containing 1 N heteroatom, wherein the heterocyclyl is unsubstituted or substituted by one to two R 9 ;

each R 6 is independently

(1) (C 1-3 )alkyl,

(2) halo(C 1-3 )alkyl,

(3) (C 1-3 )alkoxy,

(4) halo(C 1-3 )alkoxy,

(5) (C 3-7 )cycloalkyl, unsubstituted or substituted by halo,

(6) halo,

(7) cyano,

(8) hydroxy,

(9) —NH 2 ,

(10) (C 1-3 )alkyl-COOH, or

(11) (C 1-3 )alkyl-COO(C 1-4 )alkyl;

each R 7 is independently

(1) (C 1-3 )alkoxy,

(2) halo,

(3) hydroxy, or

(4) (C 1-3 )alkyl;

R 8a and R 8b are independently

(1) hydrogen,

(2) (C 1-3 )alkyl, or

(3) (C 3-7 )cycloalkyl; and

R 9 is

(1) (C 1-3 )alkyl,

(2) halo(C 1-3 )alkyl, or

(3) hydroxyl.

2. The method of claim 1 , wherein R 3 is:

(1) aryl unsubstituted or substituted by one, two, or three R 6 , or

(2) five- or six-membered heteroaryl containing one, two, or three heteroatoms independently selected from N, O and S, wherein heteroaryl is unsubstituted or substituted by one, two, or three R 6 ;

in the compound administered to the patient.

3. The method of claim 2 , wherein R 3 is aryl unsubstituted or substituted by one, two, or three R 6 in the compound administered to the patient.

4. The method of claim 1 , wherein R 1 is (C 1-6 )alkyl, halo(C 1-6 )alkyl, or —(C 1-3 )alkyl-aryl, wherein aryl is unsubstituted or substituted by one, two, or three R 7 in the compound administered to the patient.

5. The method of claim 1 , wherein R 5 is hydroxyl in the compound administered to the patient.

6. The method of claim 5 , wherein R 1 is (C 1-6 )alkyl, halo(C 1-6 )alkyl, or —(C 1-3 )alkyl-aryl, wherein aryl is unsubstituted or substituted by one, two, or three R 7 in the compound administered to the patient.

7. The method of claim 1 , wherein the compound administered to the patient is:

4-amino-5-(4-fluorophenyl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-(trifluoromethyl)pyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-chloropyridin-2-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-fluoropyridin-2-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-chloro-3-fluorophenyl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(3,4-difluorophenyl)-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-chloropyridin-2-yl)-5-cyclopropyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-fluoropyridin-3-yl)-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-fluoropyridin-3-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-chlorophenyl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(pyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

(12) 4-amino-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-phenyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(6-cyclopropylpyridin-3-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(3-fluorophenyl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-(trifluoromethyl)pyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(6-(1,1-difluoroethyl)pyridin-3-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-methylpyridin-2-yl)-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

6-(4-amino-5-methyl-6-oxo-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-5-yl)nicotinonitrile,

4-amino-5-methyl-5-(5-methylpyridin-2-yl)-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(1-isopropyl-1H-1,2,3-triazol-4-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-methylpyrazin-2-yl)-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-fluoropyridin-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-fluorophenyl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-(trifluoromethyl)phenyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-(trifluoromethyl)pyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-chloropyridin-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-chloropyridin-2-yl)-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-chloro-3-fluorophenyl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-chlorophenyl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(4-fluorophenyl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-chlorophenyl)-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(3,4-difluorophenyl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-chloro-3-fluorophenyl)-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-fluoropyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-(trifluoromethyl)phenyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-methyl-5-(pyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-methyl-5-phenyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(3,4-difluorophenyl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-methoxypyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-methoxypyridin-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-chloropyrimidin-2-yl)-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(3-chloro-4-fluorophenyl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-(difluoromethyl)pyridin-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-(difluoromethyl)pyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(6-(1,1-difluoroethyl)pyridin-3-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-methyl-5-(5-methylpyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-methylpyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

6-(4-amino-5-methyl-6-oxo-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-5-yl)nicotinonitrile,

4-amino-5-methyl-5-(6-methyl-5-(trifluoromethyl)pyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-(trifluoromethyl)pyrazin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-(trifluoromethyl)pyrimidin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-fluorophenyl)-5-methyl-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-chlorophenyl)-5-methyl-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-fluoropyridin-2-yl)-5-methyl-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(5-fluoropyridin-2-yl)-4-hydroxy-5-methyl-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-(trifluoromethyl)pyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-chloropyridin-2-yl)-5-cyclopropyl-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(3,4-difluorophenyl)-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-fluoropyridin-2-yl)-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-fluorophenyl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-fluoropyridin-2-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-chloro-3-fluorophenyl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-chlorophenyl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(3,4-difluorophenyl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-cyclopropyl-5-(3,4-difluorophenyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-cyclopropyl-5-(5-fluoropyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-methyl-5-(5-(trifluoromethyl)pyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-chloropyridin-2-yl)-5-cyclopropyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-chloropyridin-2-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-cyclopropyl-5-(5-(trifluoromethyl)pyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-methyl-5-(5-methylpyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-cyclopropyl-5-(5-methylpyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-fluorophenyl)-2-(8-isobutyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-fluorophenyl)-5-methyl-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-chloro-3-fluorophenyl)-5-methyl-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-chlorophenyl)-5-methyl-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-methyl-5-(4-(trifluoromethyl)phenyl)-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-methyl-5-(5-(trifluoromethyl)pyridin-2-yl)-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-chloropyridin-2-yl)-5-methyl-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-(trifluoromethyl)pyridin-2-yl)-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-fluoropyridin-2-yl)-5-methyl-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-chloropyridin-2-yl)-5-cyclopropyl-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(3,4-difluorophenyl)-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(3,4-difluorophenyl)-5-methyl-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-(4-fluorobenzyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-fluorophenyl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-fluorophenyl)-2-(8-(3-methoxybenzyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-(4-fluorobenzyl)-2-methyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-fluorophenyl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-fluorophenyl)-5-methyl-2-(2-methyl-8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-fluoropyridin-2-yl)-5-methyl-2-(2-methyl-8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-chloro-3-fluorophenyl)-5-methyl-2-(2-methyl-8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-fluorophenyl)-5-methyl-2-(2-methyl-8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-fluoropyridin-2-yl)-5-methyl-2-(2-methyl-8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-chlorophenyl)-5-methyl-2-(2-methyl-8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

2-([1,2,4]triazolo[1,5-a]pyrazin-6-yl)-4-amino-5-(4-chlorophenyl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(1-cyclopropyl-1H-1,2,3-triazol-4-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(1-cyclopropyl-1H-1,2,3-triazol-4-yl)-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-Amino-5-methyl-5-(5-methyl-1,3,4-oxadiazol-2-yl)-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-(difluoromethyl)-1,3,4-oxadiazol-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-methyl-5-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-5-methyl-2-(2-methyl-8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-cyclopropyl-5-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-(trifluoromethyl)-1,3,4-oxadiazol-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-cyclopropyl-1,3,4-oxadiazol-2-yl)-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-(1-fluorocyclopropyl)-1,3,4-oxadiazol-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-(1-fluorocyclopropyl)-1,3,4-oxadiazol-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(5-hydroxypyridin-2-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one,

4-amino-5-(5-hydroxypyridin-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-5-(5-hydroxypyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-(4-fluorophenyl)-2-(8-(3-hydroxybenzyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-5-cyclopropyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(pyridin-2-yl)-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one,

4-amino-5-cyclopropyl-5-(pyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-amino-2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-cyclopropyl-5-(pyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

6-(4-amino-5-cyclopropyl-6-oxo-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-5-yl)nicotinonitrile,

6-(4-amino-5-cyclopropyl-6-oxo-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-5-yl)nicotinonitrile,

5-(4-fluorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(5-chloropyridin-2-yl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-chloro-3-fluorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(5-fluoropyridin-2-yl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-cyclopropyl-5-(3,4-difluorophenyl)-4-hydroxy-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-cyclopropyl-5-(5-fluoropyridin-3-yl)-4-hydroxy-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(5-fluoropyridin-3-yl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-chlorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(pyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-phenyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(3-fluorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one,

4-hydroxy-5-methyl-5-(5-methylpyridin-2-yl)-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

6-(4-hydroxy-5-methyl-6-oxo-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidin-5-yl)nicotinonitrile,

5-(4-chloro-3-fluorophenyl)-4-hydroxy-5-methyl-2-(2-methyl-8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-fluorophenyl)-4-hydroxy-5-methyl-2-(2-methyl-8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(5-chloropyridin-2-yl)-4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-fluorophenyl)-4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(5-fluoropyridin-2-yl)-4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-(trifluoromethyl)phenyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-chloro-3-fluorophenyl)-4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-cyclopropyl-5-(4-fluorophenyl)-4-hydroxy-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-chlorophenyl)-5-cyclopropyl-4-hydroxy-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-cyclopropyl-5-(3,4-difluorophenyl)-4-hydroxy-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-chlorophenyl)-4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-hydroxy-5-methyl-5-phenyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-cyclopropyl-4-hydroxy-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-(trifluoromethyl)phenyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-hydroxy-5-methyl-5-(pyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(3,4-difluorophenyl)-4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(3-chloro-4-fluorophenyl)-4-hydroxy-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one

4-hydroxy-5-(5-methoxypyridin-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

4-hydroxy-5-methyl-5-(5-methylpyridin-2-yl)-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-cyclopropyl-5-(5-fluoropyridin-2-yl)-4-hydroxy-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one,

5-(4-fluorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-chlorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-chloro-3-fluorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-fluorophenyl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-fluoropyridin-2-yl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-chloro-3-fluorophenyl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-chlorophenyl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(3,4-difluorophenyl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-4-hydroxy-5-methyl-5-(5-(trifluoromethyl)pyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-chloropyridin-2-yl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-4-hydroxy-5-methyl-5-(5-methylpyridin-2-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

2-(8-(4-fluorobenzyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(4-fluorophenyl)-4-hydroxy-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-fluorophenyl)-4-hydroxy-2-(8-isobutyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-chlorophenyl)-4-hydroxy-5-methyl-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-fluorophenyl)-4-hydroxy-5-methyl-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-chloro-3-fluorophenyl)-4-hydroxy-5-methyl-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-cyclopropyl-5-(3,4-difluorophenyl)-4-hydroxy-2-(8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-chlorophenyl)-4-hydroxy-5-methyl-2-(2-methyl-8-propyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(3,4-difluorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one,

5-(2-fluorophenyl)-4-hydroxy-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one,

2-(8-butyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(3-fluorophenyl)-4-hydroxy-5-methyl-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one,

5-(4-Fluorophenyl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-fluorophenyl)-2-(8-isobutyl-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-methyl-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-fluorophenyl)-5-methyl-2-(8-(3,3,3-trifluoropropyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(5-chloropyridin-2-yl)-5-methyl-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(5-fluoropyridin-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

5-(4-fluorophenyl)-5-methyl-6-oxo-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-4-carboxamide,

5-cyclopropyl-6-oxo-2-(8-(3,3,4,4,4-pentafluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-(trifluoromethyl)pyridin-2-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-4-carboxamide,

5-methyl-6-oxo-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-(trifluoromethyl)pyridin-2-yl)-6,7-dihydro-5H-pyrrolo[2,3-d]pyrimidine-4-carboxamide,

4-amino-5-cyclopropyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5-(5-(trifluoromethyl)pyrimidin-2-yl)-5,7-dihydro-6H-pyrrolo[2,3-d]pyrimidin-6-one, or

4-hydroxy-5-(5-(difluoromethyl)pyridin-2-yl)-5-methyl-2-(8-(4,4,4-trifluorobutyl)-[1,2,4]triazolo[1,5-a]pyrazin-6-yl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one,

or a pharmaceutically acceptable salt thereof.

8. The method of claim 1 further comprising one or more additional active agents selected from camphor, menthol, a topical emollient, a methotrexate, chlorambucil, mycophenolate mofetil, cyclosporine, FK506, cyclophosphamide, a statin, a tyrosine kinase inhibitor, an angiotensin converting enzyme inhibitor, an angiotensin II receptor antagonist, a calcium channel blocker, omeprazole, D-penicillamine, interferon alfa, interferon gamma, aspirin, pancrealipase, a fat soluble vitamin, pulmozyme, ivacaftor, vacaftor, gentamycin, aztronam, colistin, tobramycin, a fluoroquinoline, piperacillin, chloramphenicol, sulfamethoxazole, trimethoprim, cephalexin, ceftazidime, nintedanib, N-acetylcysteine, azathioprine, tocilizumab, or pirfenidone.

9. The method of claim 1 , wherein the compound administered to the patient is

or a pharmaceutically acceptable salt thereof.